6-24133474-A-G

Variant names:

• chr6-24133474-A-G
• rs7455023
• NM_080723.5:c.-9-845A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080723.5(NRSN1):​c.-9-845A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 152,060 control chromosomes in the GnomAD database, including 19,466 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.50 (19466 hom., cov: 33)
• Consequence: NRSN1 NM_080723.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.213
• Publications: 4 publications found

Genes affected

NRSN1 (HGNC:17881): (neurensin 1) Predicted to be involved in nervous system development. Predicted to be located in cytoplasmic vesicle and growth cone. Predicted to be active in neuron projection; neuronal cell body; and transport vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRSN1	NM_080723.5	c.-9-845A>G		intron_variant	Intron 2 of 3	ENST00000378491.9	NP_542454.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRSN1	ENST00000378491.9	c.-9-845A>G		intron_variant	Intron 2 of 3	1	NM_080723.5	ENSP00000367752.4
NRSN1	ENST00000378478.5	c.-9-845A>G		intron_variant	Intron 2 of 3	1		ENSP00000367739.2
NRSN1	ENST00000378477.2	c.-9-845A>G		intron_variant	Intron 2 of 3	1		ENSP00000367738.2
NRSN1	ENST00000468195.2	n.59-845A>G		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75525 AN: 151942 Hom.: 19435 Cov.: 33

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.517

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.497 AC: 75603 AN: 152060 Hom.: 19466 Cov.: 33 AF XY: 0.498 AC XY: 37022 AN XY: 74310

African (AFR) AF: 0.599 AC: 24829 AN: 41478

American (AMR) AF: 0.473 AC: 7227 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1653 AN: 3472

East Asian (EAS) AF: 0.775 AC: 4009 AN: 5170

South Asian (SAS) AF: 0.553 AC: 2662 AN: 4812

European-Finnish (FIN) AF: 0.402 AC: 4240 AN: 10554

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29353 AN: 67964

Other (OTH) AF: 0.520 AC: 1099 AN: 2112

Alfa AF: 0.461 Hom.: 24391

Bravo AF: 0.510

Asia WGS AF: 0.654 AC: 2274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.25
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7455023; hg19: chr6-24133702;